Let’s assume an adrenal tumor has been confirmed with either blood testing, imaging, or both. Two questions must be answered next:

• Is the tumor benign or malignant?
• Should you choose surgical treatment or medical management?

Benign vs. Malignant

While only approximately 15% of canine Cushing’s syndrome patients have adrenal tumors, half of them will have benign tumors and half will have malignant ones. The choice of therapy may well depend on which one the patient has.

If imaging has not yet been performed, this is the time to do so. Chest radiographs will be important as malignant adrenal tumors tend to spread to the chest. If such spread is seen, the tumor can be assumed to be malignant. Absence of such findings, however, does not mean the tumor is benign. Ultrasound of the abdomen, if this has not already been done, (or even CT scanning, MRI imaging, or nuclear medicine scanning) will be needed to determine the size of the tumor, and to check for invasion of local abdominal tissues (especially in the liver).

Between evaluation of the chest and the abdomen, it may be possible to non-invasively determine if the tumor is malignant. It should be noted that the absence of tumor spread does not mean that the tumor is benign. If there is obvious spread to other organs, medical management is the only meaningful hope for the patient. Discuss with your veterinarian whether a referral to an oncologist for the most current medication plan is in your pet’s best interest.

What if Imaging Fails to Confirm That the Tumor Is Malignant?

As mentioned, it is not possible to say that the tumor is benign simply because tumor spread has not been detected. Still, no evidence of spread is about as close to determining that the tumor is benign as we can get without actually obtaining tissue samples. If the adrenal tumor is benign, there is an excellent chance for complete recovery if the tumor is surgically removed. The smaller the tumor, the easier the surgery, though the surgery involves delicate tissue in a difficult area.

What if Imaging Indicates the Tumor Is Malignant?

If there is obvious tumor spread, surgery may be too risky. The decision to proceed with medical therapy will depend on how debilitated the patient is, and the degree of tumor spread versus the severity of the clinical signs of Cushing’s disease. Relief, but not cure, of the clinical signs may be achieved by removing part of the tumor. Medical management with trilostane or with high doses of lysodren would be fair alternatives.

What You Should Know About Surgery

• Removing the adrenal gland is a relatively difficult surgery and may be best left to board surgeons who perform this surgery with some regularity. (The adrenal gland is located between the aorta, which is the body’s largest artery; the renal artery and vein, which are the sole blood supply to the kidney; and the phrenicoabdominal artery. This vascular area is half-jokingly referred to by surgeons as the Bermuda triangle. Surgery here is not for the inexperienced.) Removing an adrenal tumor is generally considered to be one of the most difficult surgeries in veterinary practice.
  
• Risk of bleeding is higher for larger tumors, especially if they are malignant and have invaded local structures. It is quite possible that the full extent of such invasion will not be apparent prior to surgery.

• Adrenal tissue is notoriously difficult for pathologists to grade as benign or malignant. It is possible that a tumor initially graded as benign will later turn out to be malignant.
  
• In a statistical survey of 63 dogs undergoing surgery for adrenal tumors:
  • 6% (4) had inoperable tumors and were euthanized on the surgery table.
  • 29% (18) died either in surgery or shortly thereafter due to complications.

Medical Therapy for the Adrenal Tumor

As can be seen from the above discussion, adrenalectomy is a high-risk surgery. It may not be a good choice for an elderly debilitated patient, especially if the tumor is large or has evidence of spread. Further, a 24-hour specialty center is usually needed for this sophisticated procedure and these centers may not be accessible, plus there is a great deal of expense involved in a surgical adventure of this magnitude. For these reasons, medical management may be selected as an alternative.

Lysodren is a chemotherapy drug that is able to erode the cortisol-producing layers of the adrenal gland. This ability has made lysodren, for decades the traditional medication for treating pituitary Cushing’s disease, helpful in treating adrenal tumors as well. It turns out the adrenal tumors will respond to higher doses, The higher doses needed to control adrenal tumors tend to produce more lysodren reactions than are seen when treating pituitary tumors. The average survival time for this type of therapy is 16 months.

Trilostane can also be used for functioning adrenal tumors though it will not actually diminish adrenal tissue (which could potentially diminish the tumor). Trilostane acts by inactivating excess steroid hormones and thereby managing the symptoms of Cushing’s disease. You would think that this would not be effective since it does not directly affect the tumor, but at least one study showed a comparable survival time to that of patients on lysodren. As with lysodren, a protocol is needed that is different from those using the same drugs to treat pituitary-dependent Cushing’s disease.

Something Different: Hypofractionated Stereotactic Radiotherapy

A study presented in 2014 by a group of Italian researchers treated 12 dogs with adrenal tumors with this special type of radiotherapy and all 12 of them responded. After 12 months, 11 patients were not only still alive but their Cushing’s syndromes were controlled as well (the 12th patient had died of unrelated causes). This type of therapy was considered to be far less risky than surgery and the researchers recommended further investigation. Stereotactic radiotherapy involves highly specialized equipment and is not readily available but might be worth travel depending on where it might be located. An oncologist should be consulted for more information.

Alopecia is the medical term for baldness. The term does not specify a particular type, pattern or cause of baldness; it is a general term. There are many types of alopecia/baldness. One particular type of baldness has been described in the Nordic or plush-coated breeds whereby the dog develops coat loss on the main body as well as darkly pigmented skin in the bald areas. The legs and head are generally spared and retain a normal coat.

Alopecia X goes by many names:

• Black skin disease 
• Growth hormone-responsive alopecia 
• Castration-responsive alopecia 
• The coat funk 
• Pseudo-Cushing syndrome 
• Biopsy-responsive alopecia 
• Follicular dysplasia of the Siberian husky 
• Adrenal sex hormone alopecia 
• Hair cycle arrest

The following is what is currently believed about this confusing condition.

The good news is that alopecia X is a cosmetic condition only. There is no downside to the dog except for looking funny. For this reason, treatment with medications is frequently discouraged because drugs can have bodywide effects while the disease itself has none. Furthermore, treatment has been fraught with partial responses and can be frustrating if not expensive, depending on what therapy is selected.

The skin biopsy is particularly important in making a diagnosis of alopecia X. If possible, a pathologist who specializes in reading skin tissue should be requested. The biopsy will identify structures typical of alopecia X hair follicles and help rule out concurrent allergy or infection that might mimic alopecia X.

The University of Tennessee Hormone Profile

One option in the pursuit of effective alopecia X therapy is the adrenal sex hormone panel available at the University of Tennessee. This test is done by drawing a baseline blood panel, administering a pituitary hormone called ACTH, and drawing a second blood sample an hour later to compare. Samples are shipped to Tennessee for evaluation for numerous adrenal sex hormones. The results show not only which hormones respond abnormally but the university will make suggestions as to which therapy might be likely to work.

Testing is not inexpensive and results can take several weeks to obtain but may help in selecting what therapy makes sense to try next. Often, results are ambiguous and difficult to interpret. Different specialists have different opinions on the usefulness of information obtained. This blood test may be recommended by your veterinarian as part of the alopecia X work up so we mention it here.

The Typical Patient    

The typical Alopecia X patient is a Spitz or Nordic breed such as an American Eskimo, Chow Chow, Pomeranian, Alaskan Malamute, Elkhound, or similar. Poodles have also been over-represented. Hair loss begins in early adulthood, usually by age three years. First, the long primary hairs go, leaving a fuzzy, puppy-like coat but eventually that goes, too. The bald skin becomes hyperpigmented but is not itchy, and the skin does not usually get infected.

Diagnostic Testing

Part of the problem is that all hormone-based hair losses can look exactly like this, so some testing is needed to determine which of several conditions are occurring.

Expect your veterinarian to begin with:

• A blood panel 
• A urinalysis 
• Some kind of thyroid testing 
• Some kind of adrenal hormone testing 
• A skin biopsy

The purpose of this rather broad testing is to rule out diseases that look like alopecia X but for which well-defined treatment protocols exist. This means that two conditions must absolutely be ruled out before proceeding with the trial and error process of alopecia X treatment.

• Cushing’s disease
• Hypothyroidism

Both these hormone imbalances lead to endocrine alopecia and while they look like alopecia X, they have their own specific treatments.

For this reason, the first step in treatment is to sterilize the patient; unspayed females should be spayed, and intact males should be neutered. There are health benefits to sterilization regardless of whether or not there is a hair loss issue, and many animals will grow their hair back (though possibly not permanently) so this is where we start rather than investing in complex and confusing diagnostics. If this does not work or the pet is already sterilized, then we move on to melatonin supplementation.

Melatonin

Melatonin can be obtained in 3 mg tablets at most health food stores or vitamin retail outlets. Approximately 40 percent of dogs will show some response within six to eight weeks. The medication should be given for at least two or three months before giving up but if hair regrowth occurs, the medication is continued until hair growth seems to have plateaued. After maximal hair regrowth has been achieved, the dose is gradually tapered down to a weekly dose over several months.

Some dogs can ultimately discontinue medication though it is important to realize that if you discontinue the medication and the hair falls out again, the condition may not be responsive to melatonin a second time. Recently melatonin implants have become available in the U.S. These are implanted in a similar manner to a microchip and dissolve under the skin over time. These can be used as an alternative to the oral product.

Melatonin Side Effects and Issues

• Melatonin has been used as a sleep aid. Some owners find the sedating side effect to be unacceptable. Consider giving it at bedtime so that drowsiness is less noticeable.
• Melantonin should not be used in diabetic patients as it has been found to create insulin resistance.
• Beware of melatonin brands containing xylitol. Xylitol is an innocuous sugar substitute for people but is a poison for dogs.

Since melatonin is a nutritional supplement, rather than a prescription medication, the FDA does not insist on the same quality control it does for drugs. There may be tremendous differences in the amount of melatonin contained in pills between brands. Nature’s Bounty® brand has been a preferred brand but any major supplement brand should be acceptable.

If neither sterilization nor melatonin have been fruitful and we know the dog does not have Cushing’s disease or hypothyroidism, then it is important to realize that the therapies left to try have potential side effects.

Consider this: Alopecia X is a cosmetic condition. It may make the dog look funny, but it does not cause harm.

You will need to weigh the potential side effects of therapy against your pet’s appearance. That said, there are other therapies that can be attempted.

Micro-Needling

Alopecia X is sometimes called biopsy responsive alopecia. After the skin biopsy samples are taken in the diagnostic process described above, some dogs will regrow a small tuft of hair in the biopsy area. The theory is that the inflammation associated with healing has awakened the hair follicles in that local area. This concept is applied more broadly with micro-needling, in which a roller of tiny needles is rolled over the skin creating tiny punctures and putting the skin into a healing mode. This procedure is widely used in human aesthetics to generate collagen, remove wrinkles and brighten skin complexion. The needles can be painful or at least uncomfortable so the patient may require sedation or numbing with topical anesthetics.

The skin is somewhat tender for a day or so after the procedure. Different studies report different success rates ranging from 40 to 90 percent. Because some discomfort is afforded the patient and sedation is typically needed, plus alopecia X is of cosmetic concern only, using this treatment is somewhat controversial.

Deslorelin Implants

Deslorelin is a veterinary hormone that curtails the production of estrogen and testosterone and is usually used to time ovulation in mares. It is available as an implant and was recently tested in alopecia X. Within three months, 60 percent of the unneutered male dogs experienced hair regrowth. None of the spayed females experienced hair regrowth. No side effects were noted during the one-year period of testing. This may pan out as a treatment strategy for unneutered male dogs.

Medroxyprogesterone Acetate

Injections of this long-acting progesterone were used monthly for four months in a group of Pomeranians with alopecia X. Some responded partially, one completely regrew hair, and some did not respond at all. None of the dogs had side effects during the time of the study; however, progestins are famous for inducing mammary tumors, uterine infections, and diabetes mellitus so their use should be weighed against their potential for problems.

Trilostane

Cushing’s disease is a disease of adrenal cortisone excess. The production of cortisone is complex and some of the pathways are common to sex-hormone production. For this reason, therapy for Cushing’s disease sometimes works on alopecia X. Trilostane is a medication used to treat Cushing’s disease to suppress steroid hormone production, which includes the sex steroids. Trilostane has the potential to create a dangerous deficiency in adrenal steroids so it is not without risk even though it has been effective in causing hair regrowth in some patients.

Alopecia X is a frustrating condition and will remain frustrating for years to come. Research is ongoing and progress comes gradually.